L-tetrahydropalmatine (THP), also known as rotundine, which is an alkaloid extracted from dried tubers of the plant Corydalis, a member of the poppy family, having various therapeutic effects such as sedation, hypnosis and analgesia, clinically useful in the treatment of headache, menstrual pain and insomnia.

Recent studies have found that L-tetrahydropalmatine has better analgesic effects on neuropathic pain (NPP), inflammatory pain, cancer-induced pain and antitumor drug-induced pain. Taking L-tetrahydropalmatine for long periods of time does not lead to addiction, and has better effect on overcoming cocaine addiction, methamphetamine addiction, opioid or drug addiction, alcohol addiction, smoking addition, etc.
However, L-tetrahydropalmatine leads to cardiac side effects such as reducing blood pressure, slowing heart rate, etc. It can also cause hepatotoxicity such as elevated transaminases, etc. Moreover, great individual differences in the effects of L-tetrahydropalmatine cause the uncontrollability of safety and efficacy of drugs.
The present disclosure relates to novel deuterated derivatives of L-tetrahydropalmatine. These deuterated derivatives not only markedly improve pharmacological effects, but also significantly reduce cardiac side effects, hepatotoxicity, and remarkably decrease individual differences.